Non-SMC Condensin I Complex, Subunit G (NCAPG) is a Novel Mitotic Gene Required for Hepatocellular Cancer Cell Proliferation and Migration

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Currently, only chemoembolization and sorafenib have shown survival benefits for advanced HCC. There are major unmet needs in HCC management and the discovery of new therapeutic targets. Here we identified NCAPG (non-SMC condensin I complex, subunit G) as a novel mitotic gene required for HCC cell proliferation and migration through siRNA knockdown of a panel of novel overexpressed genes in HCC based on The Cancer Genome Atlas (TCGA) dataset. We found that knockdown of NCAPG induces HCC cell mitosis and inhibits cell growth, proliferation, and migration in vitro. Tetracycline-inducible shRNA knockdown of NCAPG inhibits tumor growth of HCC cells in vivo. Moreover, overexpression of NCAPG in clinical HCC samples was associated with recurrence and survival of patients. The overexpression of NCAPG was significantly correlated with the overexpression of CCNB1 (G2/mitotic-specific cyclin B1), a regulatory protein involved in mitosis. Therefore, NCAPG may provide a promising novel therapeutic target for the treatment of advanced HCC in the future.

Non‐SMC condensin I complex subunit H enhances proliferation, migration, and invasion of hepatocellular carcinoma

“…Increasing evidence confirms that abnormalities in the non‐SMC condensin I complex are associated with the progression of HCC . NCAPH is one of the three non‐SMC subunits in the condensin I complex and plays an essential role in condensin complex stability and the resolution of sister chromatids .…”

“…Increasing evidence confirms that abnormalities in the non-SMC condensin I complex are associated with the progression of HCC. 8 NCAPH is one of the three non-SMC subunits in the condensin I complex and plays an essential role in condensin complex stability and the resolution of sister chromatids. 9 To the best of our knowledge, our study presents the first evidence that NCAPH expression is upregulated in HCC tissues and cell lines, which is consistent with the data from the GEO dataset.…”

“…The condensin I complex comprises structural maintenance of chromosome (SMC) proteins and three non‐SMC subunits, including non‐SMC condensing I complex subunit H (NCAPH), non‐SMC condensing I complex subunit G, and non‐SMC condensing I complex subunit D2 . Previous studies have reported that the abnormal expression of the non‐SMC condensin I complex is involved in the progression of human cancer . NCAPH encodes a regulatory subunit in the non‐SMC condensing I complex and is required for the conversion of interphase chromatin into condensed chromosomes .…”

“…6 Previous studies have reported that the abnormal expression of the non-SMC condensin I complex is involved in the progression of human cancer. 7,8 NCAPH encodes a regulatory subunit in the non-SMC condensing I complex and is required for the conversion of interphase chromatin into condensed chromosomes. 9 Previous studies have revealed that abnormal expression of NCAPH is associated with colon cancer and prostate cancer.…”

Transcription factor Sp1 regulates mitotic fidelity through Aurora B kinase-mediated condensin I localization

“…Zhang et al, 2020). Overexpression of another condensin complex I subunit, nCAP-G, is associated with multidrug resistance in colorectal cancer and proliferation and migration in hepatocellular carcinoma (Q. Zhang, Su, Shan, Gao, & Wu, 2018). Similarly, upregulation of condensin complex I subunit nCAP-H is associated with drug resistance and decreased diseasefree survival in oral squamous cell carcinoma (Shimomura, Sasahira, Nakashima, Kurihara- Shimomura, & Kirita, 2019).…”